Context: Knee injury is a common problem for runners. Knee pain is a common symptom in knee injury and is associated with alterations in knee and hip muscle activation and hip joint angles. Relieving pain through intervention may help to restore neuromuscular function. Objective: To examine the effects of ice and transcutaneous electrical nerve stimulation (TENS) combination treatment on perceived knee pain, hip frontal plane angle, and muscle activation during running in individuals with experimental knee pain (EKP). Design: Crossover. Setting: Laboratory. Subjects: 19 participants (11 males and 8 females, 23.2 ± 1.9 y, 176 ± 11.6 cm, 71.5 ± 16.9 kg; right leg dominant). Interventions: Hypertonic saline was infused into the infrapatellar fat pad for 74 minutes (total 11.1 mL). Subjects underwent 2 treatment conditions (sham; ice/TENS combination). Measurements were recorded during running at 4 time points (preinfusion, postinfusion, posttreatment, and postinterval). Main Outcome Measures: Perceived knee pain on a 100-mm visual analog scale (VAS), knee and hip muscle peak electromyography (EMG) amplitude, and hip adduction angles. Results: Hypertonic saline infusion increased perceived anterior knee pain in all participants. The average of peak perceived knee pain was 28 mm on a 100-mm VAS in EKP application. While the increased perceived knee pain level stayed consistent across time in the sham session, ice/TENS combination treatment significantly reduced perceived knee pain by 35% at 6 minutes after the treatment start (p = 0.049), and the reduced knee pain lasted for 22 minutes (p > 0.05). Peak EMG amplitude of the gluteus medius was decreased by 13.5% and 14.3% (p = 0.023; p = 0.013) during running after EKP in sham and treatment sessions, respectively. However, the peak EMG amplitude was not restored to pain-free level during running after the treatment (p = 0.026). No other muscles changed their peak EMG amplitude due to EKP or treatment. Hip adduction angles during running were also not altered by EKP or treatment (p > 0.3) in both sham and treatment sessions. Conclusions: EKP increased perceived knee pain and decreased peak muscle activation of the gluteus medius during running. Ice/TENS combination treatment reduced perceived knee pain quickly, but did not restore neuromechanics during running.

Formation of advanced glycation endproducts (AGEs) on proteins has been linked to the pathogenesis of diabetic complications. Importantly, elevated levels of methylglyoxal (MG) occur in type 2 diabetes mellitus (T2DM), and the resulting site-specific formation of stable adducts on arginine residues can cause protein damage. Using MG, site-specific modifications on the plasma protein plasminogen (Pg) were determined following protein digestion into peptides and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, and 30 arginine sites were identified on the protein. Investigation into three of the most highly modified sites, R504, R530, and R561, using molecular modeling, identified likely functional changes to the Pg cleavage and the lysine binding pocket as a result of adduct formation at these sites. Overall functional changes to Pg were examined using silver staining and kinetic assays to examine normal protein cleavage by activator enzymes streptokinase (STK), tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA). MG-modified Pg exhibited decreased activation into plasmin (Pn), which is the active enzyme that forms via normal Pg cleavage, by all three activator enzymes. Activation into Pn by STK was significantly delayed by MG modification on plasminogen. Similar effects were observed with tPA and uPA. Efforts to identify the primary sites of MG adduction on Pg by two dimensional gel electrophoresis (2DGE) identified six sites, including R504 and R530, as the earliest modified sites. In order to probe MG site specific modification effects on lysine binding, MG-modified protein was run through a lysine-sepharose binding column and fractions were collected. The results indicated that MG-modified Pg bound more weakly to the column and eluted easier than unmodified Pg and LC-MS/MS using a LTQ Orbitrap Velos of the fraction indicated that R504 and R530 were the primary sites of MG adduction within the eluate. To assess MG-modification of Pg in humans, 12 plasma samples were immunodepleted of the top 14 abundant proteins and samples were analyzed by LC-MS/MS using a LTQ Orbitrap Velos. Nine of the 12 patient samples indicated the presence of MG-modified peptides. The antihyperglycemic drug metformin, a drug that scavenges MG and lowers formation of AGEs, was studied in order to better elucidate this scavenging mechanism. A novel reaction imidazolinone product, IMZ, was determined to be the primary product formed in the reaction between metformin and MG, confirmed unequivocally through x-ray diffraction analysis. In order to determine levels of IMZ in human patients on metformin therapy, multiple reaction monitoring (MRM) was employed to quantify the compound. Human urine samples from 92 patients on metformin treatment were analyzed. 66 of the 68 patients to exhibit high concentrations of metformin also indicated the presence of IMZ in their urine. The remaining samples either exhibited no metformin, or levels of metformin too low to detect the presence of IMZ. Importantly, IMZ was never identified in patients without a metformin signal, indicating the validity and quality of the assay. This dissertation builds upon the current knowledge of site-specific MG modifications, both in vitro, identifying for the first time Pg as a sensitive site-specific target of glycation, with functional effects, and importantly in humans, as this is the first identification of MG-modified Pg in vivo. The functional effects associated with this modification may provide a link between elevated MG in T2DM, and resulting cardiovascular complications. Additionally, the identification of the novel reaction product IMZ is important, as it helps to fully elucidate the role metformin plays in treating T2DM patients. The detection of IMZ in the urine of human patients on metformin therapy indicates that metformin plays a role in the reducing MG levels through scavenging in vivo, and the developed MRM method allows for future rapid, sensitive study of cohorts to better understand this mechanism and the role it plays in reducing AGEs and diabetic complications.

Defining the mechanics and consequences of protein adduction is crucial to understanding the toxicity of reactive electrophiles. Application of tandem mass spectrometry and data analysis algorithms enables detection and mapping of chemical adducts at the level of amino acid sequence. Nevertheless, detection of adducts does not indicate relative reactivity of different sites. In this dissertation I describe a method to measure the kinetics of competing adduction reactions at different sites on the same protein using quantitative mass spectrometry. Adducts are formed by electrophiles at Cys-14 and Cys-47 on the metabolic enzyme glutathione-S-transferase P1-1 and accompanied by a loss of enzymatic activity. Relative quantitation of protein adducts was done by tagging N-termini of peptide digests with isotopically labeled phenyl isocyanate and tracking the ratio of light-tagged peptide adducts to heavy-tagged reference samples. This method was used to measure rate constants for adduction at both positions with two different model electrophiles, IAB and BMCC. The results indicate that Cys-47 was approximately 2-3-fold more reactive toward both electrophiles than was Cys-14. This result was consistent with the relative reactivity of these electrophiles in a complex proteome system. Quantitative analyses of protein modifications provide a means of determining the reactivity and selectivity of damaging protein modifications in chemical toxicity.Another area of study explored in this dissertation is looking at the effects of protein alkylation on activating cellular signaling pathways, specifically the JNK signaling pathway. Protein adduction has been shown to be selective between different alkylating agents. It would then be reasonable to think this selectivity of adduction translates to selectivity of downstream consequences or cellular events directly tied to specific adductions. My work will show how treatment of HEK293 cells with either IAB or BMCC leads to differences in activation of JNK signaling. In addition, I've been able to show a difference in selectivity of a number of adducted targets by each alkylating agent, which are directly involved in regulation of the JNK signaling pathway. These studies illustrate not only the significance of protein adduction, but the importance for continual research to better understand their behavior in living systems.

Background: Sagittal plane external flexion moment in early stance has been reported to be both higher and lower in people with medial knee OA compared to control subjects. Purpose: Sagittal plane knee joint kinetics and kinematics were compared between people with medial compartment OA and healthy subjects. Subjects with OA and low pain scores were also compared to those with OA and moderate pain scores. Subjects: Forty people with medial knee OA and 40 age and sex matched control subjects. Method: Knee alignment and OA severity were measured from radiographs. Frontal and sagittal plane moments and knee flexion angle during gait were measured using a three dimensional motion analysis system and force plates. The Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) was used to measure pain; this score was used to divide the OA group into low pain and moderate pain OA groups. The relationship between knee flexion moment in early stance and gait speed, knee flexion angle and pain was also determined. Results: Subjects with OA had lower gait speed and cadence, and higher double limb support time. Peak knee adduction moment (first 50% of the gait cycle) was higher in the OA group. The knee flexion moment in early stance did not differ between groups; however the knee extension moment in late stance was lower in the knee OA group. The moderate pain group walked more slowly than the low pain group. The knee adduction moment, sagittal plane moments and knee flexion angle in stance did not differ between OA groups. A positive correlation was found between knee flexion moment and knee flexion angle in early stance in the knee OA group; the correlations between knee flexion moment and pain and gait speed were not significant. Conclusion: No differences were found in the knee flexion moment or stance phase knee flexion angle between the groups compared in this study, and therefore the results do not contribute to resolution of the controversy in the literature. Participants with knee OA in this study had relatively mild to moderate disease severity, which may have contributed to the non-significant findings. / Thesis (Master, Rehabilitation Science) -- Queen's University, 2009-08-27 00:37:29.466

La question de l'accès à l'eau potable reste une préoccupation majeure de tous les habitants de la Grande Comore. Dans cette île volcanique de 1025 km2, les ressources en eau proviennent d'une part des eaux météorites liées aux pluies, qui sont recueillies dans des citernes par les toits des maisons, et d'autre part des eaux souterraines résultant de l'infiltration des précipitations facilitées par la porosité des roches. Il n'existe aucun cours d'eau permanent, mais une nappe d'eau évaluée annuellement à 1 milliard de m3 entoure toute la zone côtière. Jusqu'en 1975, ces énormes réserves d'eau souterraines n'étaient pas du tout exploitées. Actuellement, la nappe alimente quelques 20 localités représentant environ 30 % de la population. Ainsi 70 % des habitants ne bénéficient pas, à l'heure actuelle, d'un accès continu à la ressource souterraine. Ils utilisent l'eau des pluies recueillie dans des citernes. Cette source d'approvisionnement n'est suffisante que pendant la saison des pluies. Au cœur de la saison sèche, qui se situe généralement de juin à novembre, l'eau doit être rationnée au sein des familles des villages du nord-est et du sud-est, régions situées sous le vent, où la saison sèche est particulièrement longue. Notre recherche de thèse se propose d'abord d'évaluer l'état de la ressource et identifier ensuite les problèmes d'accès à l'eau. Cette thèse propose des solutions pour résoudre dans une logique de développement durable le problème de l'eau en Grande Comore. / The question of access to safe drinking water has remained a big concern for the people who live in Grande Comoro and even nowadays they still cope with the problem of safe drinking water. Yet Grande Comoro presents the originality of plentiful water resources; howeever, that is not enough to avoid the water shortage that harms the population. In this volcanic island of 1025 km2, the water resources come largely from the meteorite water related to the raining, which is collected in water tanks through the roof of houses. In addition to that, the water resources also come from underground water resulting from the seepage of rainfall facilitated by the porosity of the rocks. There is no permanent stream but a sheet that surrounds the costal area. The raining water which goes underground joins a basic sheet forming a big reservoir estimated at one billion square meters. until 1975, those huge underground water reservoirs were not exploited at all. For the time being, the sheet is suppling (apart from Moroni and its suburbs) some 20 localities in the island. Overall the island, only 30 % of the population is more or less correctly supplied. Our thesis research is firstly proposing to evaluate the state of the resource, and put it in perspective with the demographic growth. Then, identifying the problems relating to the access of water in order to study the part of responsability, shared between technical, financial and political issues. This thesis is proposing solutions to resolve in a logic of sustainable development the paradox of an island "plentifully watered but in a constant situation of water shortage."

Running is known to provide important health benefits. However, the incidence of injury among runners is high, particularly among novice runners, which discourages long term participation in the sport. The knee is the most commonly injured joint in novice runners. In general, aberrant frontal and transverse plane kinematics are associated with the development of knee injuries in runners. It was unknown whether the high rate of knee injury in novice runners was due to abnormal kinematics. Further, it was unclear whether these risk factors for injury could be improved. This dissertation includes four studies investigating kinematics in novice runners, how they change with training and evaluation of a running assessment. The first study compared frontal and transverse plane kinematics of female novice and experienced runners. Novice runners displayed more knee kinematics associated with injury than experienced runners, which may contribute to their higher risk of injury. The second study investigated the effects of two different training programs on kinematics of novice runners: one program consisted of 8 weeks of walking followed by 8 weeks of running, the other consisted of 8 weeks of strength/plyometric training followed by 8 weeks of running. Results demonstrated that training produced small changes in kinematics, however all types of training produced a mix of beneficial and detrimental effects. Participants who completed the study displayed better knee kinematics 8 than those who dropped out, which may have influenced their ability to complete the program. The third study sought to investigate changes in coordination of the hip and ankle joints, and their contributions to knee joint angles thought to contribute to injury. Results demonstrated that both the hip and the ankle may influence changes in knee kinematics, however the relative motion of the hip and the ankle appears to remain stable with training. In the final study, we investigated the reliability and validity of the Running Readiness Scale (RRS), as a low cost assessment of kinematics related to injury in runners. The RRS demonstrated good inter and intra rater reliability. Further, the RRS appeared to effectively discriminate between runners according to knee abduction, but not knee internal rotation.

Behaving in novel ways is essential to the development of the types of complex performances described by the term creativity, problem solving, and perseverance. Some research suggests that response variability is an operant and a critical component of novel behavior. However, other account of novel behavior may be more parsimonious. Topographical variability has rarely been examined, nor has operant variability with organisms with baselines featuring stereotypic responding. This study examined the effects of a variability-specifying contingency on the cumulative novel responses of undergraduate students. Using the PORTL apparatus, participants interacted with a ball with a single hand. When the variability-specifying contingency was in effect, novel topographies were reinforced. When a reinforce every response condition was implemented, the participants did not emit any novel responses. When variability-specifying contingencies were in effect, novel responses were rarely followed by subsequent novel responses. They were mostly followed by repeated emission of the same topography, or by other previously emitted topographies. Novel responding did not persist long, although the variability-specifying contingency remained in effect and the potential for novel responding was great. The variability-specifying contingency often resulted in stereotypic response chains. Each of these findings call into the question the assertion that variability is an operant and suggests other possible explanations for the observed novelty.

No description available.

Patients suffering from brachial plexus injury or other spinal cord related injuries often lose their hand functionality. They need a device which can help them to perform day to day activities by restoring some form of functionality to their hands. A popular solution to this problem are robotic exoskeletons, mechanical devices that help in actuating the fingers of the patients, enabling them to grasp objects and perform other daily life activities. This thesis presents the design of a novel exoskeleton glove which is controlled by a neural network-based controller. The novel design of the glove consists of rigid double four-bar linkage mechanisms actuated through series elastic actuators (SEAs) by DC motors. It also contains a novel rotary series elastic actuator (RSEA) which uses a torsion spring to measure torque, passive abduction and adduction mechanisms, and an adjustable base. To make the exoskeleton glove grasp objects, it also needs to have a robust controller which can compute forces that needs to be applied through each finger to successfully grasp an object. The neural network is inspired from the way human hands can grasp a wide variety of objects with ease. Fingertip forces were recorded from a normal human grasping objects at different orientations. This data was used to train the neural network with a R2 value of 0.81. Once the grasp is initiated by the user, the neural network takes inputs like orientation, weight, and size of the object to estimate the force required in each of the five digits to grasp an object. These forces are then applied by the motors through the SEA and linkage mechanisms to successfully grasp an object autonomously. / Master of Science / Humans are one of the few species to have an opposable thumb which allows them to not only perform tasks which require power, but also tasks which require precision. However, unfortunately, thousands of people in the United States suffer from hand disabilities which hinder them in performing basic tasks. The RML glove v3 is a robotic exoskeleton glove which can help these patients in performing day to day activities like grasping semi-autonomously. The glove is lightweight and comfortable to use. The RML glove v3 uses a neural network based controller to predict the grasp force required to successfully grasp objects. After the user provides the required input, the glove estimates the object size and uses other inputs like object orientation and weight to estimate the grasp force in each finger linkage mechanism. The motors then drive the linkages till the required force is achieved on the fingertips and the grasp is completed.

The periodic repetitions of laryngeal adduction and abduction gestures were uttered by 16 subjects. The movement of the cuneiform tubercles was tracked over time in the laryngoscopic recordings of these utterances. The adduction velocity and abduction velocity were determined objectively by means of a piecewise linear model fitted to the cuneiform tubercle trajectories. The abduction was found to be significantly faster than the adduction. This was interpreted in terms of the biomechanics and active control by the nervous system. The biomechanical properties could be responsible for a velocity of abduction that is up to 51% higher compared to the velocity of adduction. Additionally, the adduction velocity may be actively limited to prevent an overshoot of the intended adduction degree when the vocal folds are approximated to initiate phonation.